Drijfhout W J, Brons H F, Oakley N, Hagan R M, Grol C J, Westerink B H
University Centre for Pharmacy, Department of Medicinal Chemistry, A. Deusinglaan 1, Groningen, The Netherlands.
Neuroscience. 1997 Sep;80(1):233-9. doi: 10.1016/s0306-4522(97)00080-8.
This study describes the use of the microdialysis technique to elucidate specific properties of the circadian pacemaking system in the hypothalamus, by measurement of melatonin production in the pineal gland. Melatonin has appeared to be a reliable marker of the pacemaker activity, which is influenced by the light/dark cycle. A phase shift in the light/dark cycle was applied to perturb the rhythm generating system. An 8-h phase advance resulted in the disappearance of melatonin production over two days, with basal levels comparable to normal daytime levels. In the subsequent return of rhythmic melatonin production, new clock characteristics could be revealed, due to the high time-resolution measurements of microdialysis. While half of the animals still did not show any rhythmicity, the other half of the animals regained rhythmicity with entrained onset of melatonin production, while the offset was variable and not stably entrained to lights on. Ten days after the shift, the system had completely recovered and all animals regained normal rhythmicity, in phase with the new light/dark cycle. The results are interpreted in terms of the two-oscillator model, with one oscillator reacting with a phase advance and the other with a phase delay to adapt to the phase shift.
本研究描述了通过测量松果体中褪黑素的产生，利用微透析技术来阐明下丘脑昼夜节律起搏系统的特定特性。褪黑素似乎是起搏器活动的可靠标志物，其受光/暗周期影响。对光/暗周期进行相位偏移以干扰节律产生系统。提前8小时的相位偏移导致褪黑素分泌在两天内消失，基础水平与正常白天水平相当。在随后节律性褪黑素分泌恢复的过程中，由于微透析的高时间分辨率测量，可以揭示新的时钟特性。虽然一半的动物仍未表现出任何节律性，但另一半动物随着褪黑素分泌的同步开始恢复了节律性，而结束时间是可变的，且未稳定地与光照同步。偏移十天后，系统已完全恢复，所有动物都恢复了正常节律性，与新的光/暗周期同步。结果根据双振荡器模型进行解释，其中一个振荡器以相位提前做出反应，另一个以相位延迟做出反应以适应相位偏移。
